A polypeptide possessing anti-insulin property was isolated from the urine of patients with lipoatrophic diabetes and proteinuric diabetic patients without lipoatrophy. It was not found in the urine of normal people or proteinuric subjects without diabetes. A similar polypeptide was also obtained from pituitaries of beef, hog, sheep and humans. The substance from all the above sources has an isoelectric point of pH 4.1 and was shown to be capable of inducing hyperglycemia and insulin resistance in man and dogs. Induction of hyperglycemia and hyperinsulinemia by administration of the substance to dogs has been demonstrated. Its anti-insulin property was also demonstrated in vitro. Present studies indicate that the source of the urinary diabetogenic polypeptide is the pituitary gland. The molecular weight of the urinary polypeptide from proteinuric diabetic patients is 20,800 and that from human pituitaries is 20,600. Its diabetogenic potency is much greater than that of human growth hormone. The substance from both sources has now been purified. The amino acid composition is markedly different from that of human growth hormone and prolactin. Radioimmunoassay studies have shown that the antiserum to the urinary diabetogenic peptide does not cross react with human growth hormone. The antiserum to the pituitary peptide showed some cross reactivity with human growth hormone but not with prolactin. Cross reactivity studies with other peptide hormones are in progress. BIBLIOGRAPHIC REFERENCE: Pek, S., Tai, T.Y., Fajans, S.S. and Louis, L.H.: Direct Stimulatory Effect of Bovine Growth Hormone (bGH) upon glucagon (IRG) and Insulin (IRI) Release from Rat Pancreas. Clin. Res. 23:422A (Apr) 1975.